Due to an aging society, there have been many attempts to develop orally-disintegrating tablets which can be easily taken by elderly people who have difficulty or trouble in swallowing tablets. Accordingly, there are growing demands for developing orally-disintegrating tablets containing various active ingredients. In case that an active ingredient has a bitter taste, the masking of the bitter taste may be necessary to formulate it into orally-disintegrating tablets and the like. Also, controlled release of an active ingredient may be necessary for increasing the bioavailability of the active ingredient. However, many of such functional particles tend to give some adverse affects on the formability of tablets (for example, they lack sufficient hardness when homogeneously distributed in a tablet), and thus it is necessary to add a large amount of additives such as an excipient and a binder to avoid the adverse affects, which inevitably leads the tablets to be in an inconvenient big size.
Patent Reference 1 discloses a press-coated rapidly disintegrating tablet as a unique form which has not been well known before. Press-coated tablets have a double-layered structure consisting of an inner core and an outer layer, and they have been attracting attentions as a novel technique for formulating tablets. However, the press-coated formulations disclosed in Patent Reference 1 are designed focusing on the solubility and degradability of the inner core, and the ingredients of both the inner core and the outer layer comprise ingredients with formability (for example, it appears that the ingredients of the inner core in Patent Reference 1 has formability and a certain hardness, as figured out in the results of Example 2 in which only the ingredients of the inner core were compressed into tablets). Thus, Patent Reference 1 does not try to apply powder/granular material with poor formability to the ingredients of the inner core, and the document discloses only a limited range of ingredients applicable to the inner core. Additionally, Patent Reference 1 discloses a combination of “microcrystalline cellulose” and “a sugar or a sugar alcohol” as an ingredient of the outer layer of the press-coated tablet, but it fails to disclose a combination which further comprises the “particular ingredients” of the present invention.
Furthermore, the particular ingredients of the present invention which are essential for the outer layer (e.g. carmellose, low-substituted hydroxypropylcellulose, natural starches, and/or crospovidone) are disclosed as a dissolution/disintegration accelerator of the inner core in Patent Reference 1 (see, page 9, lines 17 to 26). In detail, Patent Reference 1 explains that the outer layer comprises ingredients with good formability, and preferably it further comprises ingredients with good solubility and/or disintegrability; while the inner core also comprises ingredients with good solubility and/or disintegrability, and it may further comprise a dissolution/disintegration accelerator (see, page 8, lines 14 to 17). Moreover, Patent Reference 1 indicates that said inner core and outer layer are used to prepare a molded product having a double-layered structure wherein only the outer layer, which needs hardness, has a good formability whereas the inner core has an excellent solubility/disintegrability; and its inventors thus completed a molded product having a rapid dissolving/disintegration time with sufficient formability (see, page 5, lines 5 to 11 and abstract). Namely, it seems that the molded product in Patent Reference 1 exhibits its characteristics by containing ingredients such as dissolution/disintegration accelerators only in the inner core (i.e. excluding them from the outer layer). Conversely, the particular ingredients in the present invention are essential ingredients for the outer layer and therefore the particular ingredients in the present invention are used in an opposite manner to the ingredients in the invention of Patent Reference 1.
Patent Reference 2 discloses some trials of applying microcapsule-like granules to the ingredients of the inner core regarding the formulation in Patent Reference 1 described above. In detail, Patent Reference 2 discloses some studies on applying microcapsule-like granules to the inner core of the press-coated tablet, and some successful examples of press-coated formulations containing microcapsule-like granules in their inner cores which were prepared using the outer layers comprising lactose and microcrystalline cellulose according to a given method. Patent Reference 2 discloses an invention of press-coated tablets containing microcapsule-like granules in their inner core, but fails to disclose or suggest studies on applying the press-coated tablets to orally-disintegrating tablets. Additionally, in Patent Reference 2, there is no study about applicable ingredients for the outer layer in the press-coated formulation containing microcapsule-like granules in its inner core, other than lactose and microcrystalline cellulose. Of course, Patent Reference 2 does not disclose the combination of the essential ingredients for the outer layers of the present invention. Moreover, Patent Reference 2 fails to disclose mannitol as an ingredient of the outer layer of the press-coated formulation.
Patent Reference 3 refers to an orally disintegrating tablet comprising mannitol, but does not clearly disclose press-coated formulations.
[Patent Reference 1] WO 2003/028706 A1
[Patent Reference 2] WO 2005/097041 A1
[Patent Reference 3] JP 2001-058944 A